Alzheimer's disease and antibody-mediated immune responses to infectious diseases agents: a mendelian randomization study.

IF 2.5 3区生物学 Hereditas Pub Date : 2025-01-04 DOI:10.1186/s41065-024-00358-4

Jiayuan Zhang, Mingming Wang, Dong Wang, Linwen Deng, Yao Peng

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Abstract

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, with antibody-mediated immune responses to infectious diseases agents potentially playing a decisive role in its pathophysiological process. However, the causal relationship between antibodies and AD remains unclear.

Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal link between antibody-mediated immune responses to infectious diseases agents and the risk of AD. Genetic variations associated with these antibodies obtained from UK Biobank, and data on AD were obtained from the Finnish databases, utilizing its extensive repository of genome-wide association studies (GWAS) for a comprehensive analysis. The MR analysis employed the inverse variance-weighted, MR-Egger, and weighted median methods. Sensitivity analysis was also performed using MR-Egger regression, MR-pleiotropy residual sum, and outlier tests.

Results: Two causal associations were identified between antibody-mediated immune responses to infectious diseases agents and AD. Varicella zoster virus glycoproteins E and I antibody suggest a protective association with AD. Conversely, higher levels of Epstein-Barr virus EBNA-1 antibody appear to be associated with an increased risk of AD.

Conclusion: Our MR analysis has revealed a causal relationship between antibody-mediated immune responses to specific infectious disease agents and AD. These findings provide valuable insights into the pathophysiological mechanisms underlying AD.

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阿尔茨海默病和抗体介导的免疫反应对传染病代理：孟德尔随机研究。

背景：阿尔茨海默病（AD）是一种常见的神经退行性疾病，抗体介导的免疫反应在感染性疾病的病理生理过程中可能起着决定性作用。然而，抗体与AD之间的因果关系尚不清楚。方法：采用双样本孟德尔随机化（MR）分析，探讨抗体介导的免疫反应与AD风险之间的因果关系。与这些抗体相关的遗传变异来自UK Biobank， AD的数据来自芬兰数据库，利用其广泛的全基因组关联研究（GWAS）库进行全面分析。MR分析采用反方差加权法、MR- egger法和加权中位数法。敏感性分析还使用MR-Egger回归、mr -多效性残差和和异常值检验。结果：确定了抗体介导的对传染病病原体的免疫反应与AD之间的两个因果关系。水痘带状疱疹病毒糖蛋白E和I抗体提示与AD的保护性关联。相反，较高水平的eb病毒EBNA-1抗体似乎与阿尔茨海默病风险增加有关。结论：我们的MR分析揭示了抗体介导的对特定传染病病原体的免疫反应与AD之间的因果关系。这些发现为阿尔茨海默病的病理生理机制提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.